title: SDF-1/CXCR4 axis promotes directional migration of colorectal cancer cells through upregulation of integrin αvβ6.
abstract: Colorectal cancer (CRC) displays a predilection for metastasis to liver. Although stromal cell-derived factor-1 (SDF-1)/CXCR4 plays an important role in the liver metastasis, the molecular mechanism still remains obscure. We previously reported that integrin αvβ6 was implicated in the progression of CRC. However, no data are currently available on the cross talk between CXCR4 and αvβ6. In the present study, we first demonstrated the cross talk between CXCR4 and αvβ6 and their role in liver metastasis of CRC. We analyzed 159 human CRC samples and found that expression of CXCR4 and αvβ6 was significantly associated with liver metastasis, and interestingly expression of αvβ6 significantly correlated with expression of CXCR4. Both CXCR4 and αvβ6 were highly expressed in metastatic CRC cell lines HT-29 and WiDr, whereas both of them were exiguous in non-metastatic cell line Caco-2. Furthermore, inhibition of αvβ6 significantly decreased SDF-1α-induced cell migration in vitro. SDF-1/CXCR4 could upregulate αvβ6 expression through phosphorylation of ERK and activation of Ets-1 transcription factor. In conclusion, we demonstrate that SDF-1/CXCR4 induces directional migration and liver metastasis of CRC cells by upregulating αvβ6 through ERK/Ets-1 pathway. These data support combined inhibition of CXCR4 and αvβ6 to prevent development of liver metastasis of CRC.
authors.affiliation: Department of Hepatobiliary Surgery.
authors.forename: Ben
authors.initials: B
authors.lastname: Wang
authors.forename: Wenke
authors.initials: W
authors.lastname: Wang
authors.forename: Weibo
authors.initials: W
authors.lastname: Niu
authors.forename: Enyu
authors.initials: E
authors.lastname: Liu
authors.forename: Xiangjuan
authors.initials: X
authors.lastname: Liu
authors.forename: Jiayong
authors.initials: J
authors.lastname: Wang
authors.forename: Cheng
authors.initials: C
authors.lastname: Peng
authors.forename: Song
authors.initials: S
authors.lastname: Liu
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Niu
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D015153:Blotting, Western; D018938:Caco-2 Cells; D002465:Cell Movement; D049109:Cell Proliferation; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D024202:Electrophoretic Mobility Shift Assay; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D019073:HT29 Cells; D006801:Humans; D007124:Immunoenzyme Techniques; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000951:Antigens, Neoplasm; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D016023:Integrins; D050784:Proto-Oncogene Protein c-ets-1; D012333:RNA, Messenger; D019718:Receptors, CXCR4; C073878:integrin alphavbeta6